Document Detail


Identification of metabolic pathways of the lipid peroxidation product 4-hydroxynonenal in in situ perfused rat kidney.
MedLine Citation:
PMID:  9300788     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The metabolism of the cytotoxic lipid peroxidation product 4-hydroxynonenal was studied in perfused rat kidney. We investigated the total capacity of the rat kidney to metabolize 4-hydroxynonenal (HNE) and quantified the metabolites in the venous effluents as well as in the excreted urine. A rapid utilization of HNE was demonstrated, due to its immediate reactions with cellular compounds and its metabolism. During the first 3 min more than 80% of the infused HNE was metabolized in the perfused kidney. Glutathione-HNE conjugate (GSH-HNE: 35%), the corresponding alcohol 1,4-dihydroxynonene (1,4-DHN: 12%), HNE-mercapturic acid conjugate (HNE-MA: 4%), 4-hydroxynonenoic acid (HNA: 7%), tricarboxylic acid (TCA-cycle metabolites), and water (32%) were identified as primary and secondary metabolic products. We postulated that the total capacity of rat kidney to metabolize 4-hydroxynonenal with about 160-190 nmol/g wet wt/min. (initial influent concentration was 100 nmol/ml HNE) and other aldehydic products of lipid peroxidation is in the same range as that in other organs, e.g., intestine with 22 nmol/g wet wt/min (initial 70 nmol/ml HNE) (Siems et al. 1995. Life Sci. 57: 785-789) and heart with about 50 nmol/g wet wt/min (initial 10 nmol/ml HNE) (Grune et al. 1994. Cell Biochem. Funct. 12: 143-147). Compared to other organs, liver and kidney seemed to be the most important organs for the elimination of the final products of metabolism. The importance of the kidney in the formation of HNE-mercapturic acid conjugate was demonstrated (Alary et al. 1995. Chem. Res Toxicol. 8: 34-39). The selective excretion of this final metabolite of aldehyde metabolism may be of central importance in the detoxification of a number of lipid peroxidation products.
Authors:
T Grune; W G Siems; T Petras
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of lipid research     Volume:  38     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-10-29     Completed Date:  1997-10-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1660-5     Citation Subset:  IM    
Affiliation:
Department of Physical Therapy and Rehabilitation, Medical Faculty (Charité), Humboldt-University Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Aldehydes / administration & dosage,  metabolism*
Alkenes / metabolism
Animals
Glutathione / metabolism
Infusions, Intra-Arterial
Kidney / metabolism*
Lipid Peroxidation*
Male
Perfusion
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/1,4-dihydroxy-2-nonene; 0/Aldehydes; 0/Alkenes; 29343-52-0/4-hydroxy-2-nonenal; 70-18-8/Glutathione

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